lactoferrin and shikonin

Remodeling tumor immune microenvironment (TIME) is an important strategy to lift the immunosuppression and achieve immune normalization. In this work, a mannosylated lactoferrin nanoparticulate system (Man-LF NPs) is developed for dual-targeting biomimetic codelivery of shikonin and JQ1 via the mannose receptor and LRP-1 that are overexpressed in both cancer cells and tumor-associated macrophages. The Man-LF NPs can serve as multitarget therapy for inducing immune cell death in the cancer cells, repressing glucose metabolism and repolarizing tumor-associated macrophages, and consequently, lead to remodeling the TIME (e.g., promotion of dendritic cell maturation and CD8

Topics: Azepines; Biomimetics; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Dendritic Cells; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Lactoferrin; Lectins, C-Type; Low Density Lipoprotein Receptor-Related Protein-1; Macrophages; Mannose; Mannose Receptor; Mannose-Binding Lectins; Nanoparticles; Naphthoquinones; Neoplasms; Receptors, Cell Surface; Triazoles; Tumor Microenvironment

Shikonin (SHK) is a highly liposoluble naphthoquinone pigment has recently been investigated as a potential antiglioma agent. However, shikonin shows several limitations like poor aqueous solubility, short half-life and non-selective biodistribution. Herein, we have developed a nanoparticles (NPs) prepared from PEG-PLGA using an emulsion solvent evaporation method. Nanoparticle surfaces were modified by coating with lactoferrin (Lf) to improve the crossing of the blood brain barrier and targeting of glioma cells via receptor-mediated path-ways. X-ray powder diffraction and differential scanning calorimetry analysis revealed the amorphous nature of SHK encapsulated within the NPs. Moreover, the drug-loaded NPs exhibit narrow size distribution and high encapsulation efficiency. The in vitro release experiments of the NPs exhibited sustained release for more than 72h. When compared to free SHK and SHK/NPs, in vivo study demonstrated higher brain concentration of SHK, indicating a significant effect of Lf coated NPs on brain targeting. Accordingly, these findings provide evidence for the potential of Lf-modified NPs as a targeted delivery system for brain glioblastomas treatment.

Topics: Animals; Brain; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Glioma; Humans; Lactoferrin; Nanoparticles; Naphthoquinones; Polyesters; Polyethylene Glycols; Rats; Tissue Distribution